Supplemental funds are requested to augment the level of support of previously approved personnel in a study of fractionated large field proton therapy (parent grant #1 P01 CA 21239). The additional effort is needed in order to increase the number of patients treated by proton therapy in this program, and to permit the execution of treatment planning studies designed to compare the dose distributions possible with proton relative to conventional techniques. These activities are central to the objectives of the study which are: (1) to evaluate the potential clinical advantages of proton therapy for selected tumor-normal tissue situations through critical evaluation of comparative treatment plans and treatment of selected patients; (2) to assess the problems posed by tissue heterogeneity through theoretical calculations, use of a CT scanner in a variety of anatomic sites, and confirmatory measurements in proton beams; (3) to make improvements to the treatment facility which will permit routine treatment of a substantial number of patients with one fraction per day and with reliability of dose delivery and beam quality; (4) to measure the proton RBE for small fractionated doses with a number of end points; (5) to treat a number of patients with protons in situations in which protons appear to offer an advantage and for which the heterogeneity problem is surmountable; (6) to plan a prospective clinical trial of proton vs photon therapy; and (7) to design these clinical trials, to the extent feasible, to provide control information for work with pi-meson or heavy ion therapy. To date 68 patients have received definitive radiation therapy using proton beams. Significant numbers of patients have been treated in two categories: treatment of carcinoma of the prostate using a proton boost technique; and treatment of choroidal melanomas using protons alone. The experience with proton beams to date had been highly encouraging and makes us optimistic that protons can realize their potential for improved local control and/or reduction of morbidity for a large class of cancer patients.